Hydrolytically degradable alkylene oxide based polymers

Abstract

The present invention provides a water soluble, nonpeptidic polymer comprising two or more alkylene oxide-based oligomers linked together by hydrolytically degradable linkages such as carbonates. Typically, the oligomer portion of the polymer is an amphiphilic triblock copolymer having a central propylene oxide block or butylene oxide block positioned between two ethylene oxide blocks. The polymer can be hydrolytically degraded into oligomers under physiological conditions. In aqueous media, the polymer preferably forms thermally reversible, hydrolytically degradable hydrogels that can be used, for example, for drug delivery and related biomedical applications.

Description

[0001] This application claims the benefit of priority of U.S. Provisional Patent Application Ser. No. 60 / 357,350, the content of which is incorporated herein by reference in its entirety.FIELD OF THE INVENTION [0002] The present invention generally relates to water soluble, hydrolytically degradable, and nonpeptidic polymers. More specifically, the invention is directed to hydrolytically degradable polymers comprising oligomers of particular alkylene oxide triblock copolymers, and to compositions and uses thereof. The polymers are suitable for drug enhancement, in vivo delivery of biologically active agents, and use in medical devices. BACKGROUND OF THE INVENTION [0003] The hydrophilic polymer poly(ethylene glycol), abbreviated “PEG”, is of considerable utility in biological applications and in medicine. PEG is a polymer that is soluble in water and in many organic solvents, is non-toxic, and non-immunogenic. In recent years, the use of PEG has expanded into the biomedical, biotech...

AI Technical Summary

Benefits of technology

[0029] Also provided is (i) a polymer activated for conjugation to a biologically active agent such as a protein or peptide, and (ii) the resulting polymer conjugate. The polymer can impart desirable characteristics to a given bioactive agent such as improved water solubility, reduced immunogenicity, and longer circulating half-life, although the reverse thermal gelation characteristics of the polymer itself may be lost.

[0032] Thus, this invention provides a versatile polymer that is especially suited for forming a thermally reversible hydrogel for sustained delivery of biologically active agents. The polymer is easy to prepare and can be synthesized in large quantities. The polymer can be formed in a single reaction with multiple degradable carbonate linkages in the backbone. The hydrogel of this invention can be degraded under physiological conditions to generate oligomers of predetermined molecular weight that can be easily cleared from the body.

Problems solved by technology

Methods such as these result in gels containing non-PEG contaminants.

As a result, degradation and dissolution of the matrix can result in undesirable or toxic components being released into the bloodstream.

Further, the harsh gelling conditions employed in such methods can often inactivate or degrade drug substances incorporated in such hydrogel compositions.

Organic solvents are often toxic and irritating to tissue.

However, Poloxamer-based gels are not biodegradable, making drug release from such systems highly unpredicable.

Moreover, certain poloxamer based gels have been unsuccessful in clinical trials, due not only to performance limitations, but also due to the adverse side effects attributed to the high concentrations of polymer that must be delivered in order to achieve gelation at body temperature.

In general, the development of hydrogel formulations for drug delivery has progressed rather slowly, partially due to the problems described above and additionally due to problems associated with parenteral administration of hydrogels.

Images